Role of soluble guanylyl cyclase–cyclic GMP signaling in tumor cell proliferation

Mujoo, Kalpana; Sharin, Vladislav G.; Martin, Emil; Choi, Byungcho; Sloan, Courtney; Nikonoff, Lubov E.; Kots, Alexander Y.; Murad, Ferid

doi:10.1016/j.niox.2009.11.007

Cited by 63 publications

(52 citation statements)

References 39 publications

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“…sGC are a family of proteins composed of membrane-bound and soluble isoforms and expressed in virtually all cell types [43]. sGC catalyze conversion of the purine nucleoside guanosine-5′-triphosphate to cGMP in response to various messengers such as peptide ligands, calcium influx, and NO [44].…”

Section: Guanylyl Cyclase and Signaling By Cyclic Guanosine Monophospmentioning

confidence: 99%

Methylene Blue for Distributive Shock: A Potential New Use of an Old Antidote

2013

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Methylene blue is used primarily in the treatment of patients with methemoglobinemia. Most recently, methylene blue has been used as a treatment for refractory distributive shock from a variety of causes such as sepsis and anaphylaxis. Many studies suggest that the nitric oxidecyclic guanosine monophosphate (NO-cGMP) pathway plays a significant role in the pathophysiology of distributive shock. There are some experimental and clinical experiences with the use of methylene blue as a selective inhibitor of the NO-cGMP pathway. Methylene blue may play a role in the treatment of distributive shock when standard treatment fails.

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Section: Guanylyl Cyclase and Signaling By Cyclic Guanosine Monophospmentioning

confidence: 99%

Methylene Blue for Distributive Shock: A Potential New Use of an Old Antidote

2013

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“…Synergistic Effect of CN2-Cbi and BAY41-2272 in Intact Cells and Isolated Aorta. We tested whether CN2-Cbi activates sGC in intact breast cancer MDA468 cells, previously shown to express functional sGC (Mujoo et al, 2010). An increased intracellular cGMP level was observed when these cells were exposed to 100 M CN2-Cbi (Fig.…”

Section: Novel Regulatory Site For No Receptor 727mentioning

confidence: 99%

Cobinamides Are Novel Coactivators of Nitric Oxide Receptor That Target Soluble Guanylyl Cyclase Catalytic Domain

Sharina

Sobolevsky

Doursout³

et al. 2011

J Pharmacol Exp Ther

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Soluble guanylyl cyclase (sGC), a ubiquitously expressed hemecontaining receptor for nitric oxide (NO), is a key mediator of NOdependent processes. In addition to NO, a number of synthetic compounds that target the heme-binding region of sGC and activate it in a NO-independent fashion have been described. We report here that dicyanocobinamide (CN2-Cbi), a naturally occurring intermediate of vitamin B 12 synthesis, acts as a sGC coactivator both in vitro and in intact cells. Heme depletion or heme oxidation does not affect CN2-Cbi-dependent activation. Deletion mutagenesis demonstrates that CN2-Cbi targets a new regulatory site and functions though a novel mechanism of sGC activation. Unlike all known sGC regulators that target the N-terminal regulatory regions, CN2-Cbi directly targets the catalytic domain of sGC, resembling the effect of forskolin on adenylyl cyclases. CN2-Cbi synergistically enhances sGC activation by NO-independent regulators 3-(4-amino-5-cyclopropylpyrimidine- (cinaciguat or BAY58-2667), and 5-chloro-2-(5-chloro-thiophene-2-sulfonylamino-N-(4-(morpholine-4-sulfonyl)-phenyl)-benzamide sodium salt (ataciguat or HMR-1766). BAY41-2272 and CN2-Cbi act reciprocally by decreasing the EC 50 values. CN2-Cbi increases intracellular cGMP levels and displays vasorelaxing activity in phenylephrine-constricted rat aortic rings in an endothelium-independent manner. Both effects are synergistically potentiated by BAY41-2272. These studies uncover a new mode of sGC regulation and provide a new tool for understanding the mechanism of sGC activation and function. CN2-Cbi also offers new possibilities for its therapeutic applications in augmenting the effect of other sGC-targeting drugs.

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“…It is reported that the enhancement of a soluble form of GUCY1B3 led to the activation of the osteoclasts in the osteolytic bone metastasis process. Moreover, this protein enhances tumor growth of glioma (35) and angiogenesis in both glioma and chorioallantoic membrane (35,36), and plays paradoxical roles in the proliferation of cancer cells (37), suggesting that GUCY1B3 could be involved in bone metastasis.…”

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confidence: 99%

Identification of genes potentially involved in bone metastasis by genome-wide gene expression profile analysis of non-small cell lung cancer in mice

et al. 2012

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Abstract. Lung cancer is commonly associated with multiorgan metastasis, and the bone is a frequent metastatic site for lung cancer. However, the molecular mechanism of organspecific metastasis remains poorly understood. To elucidate this issue, we analyzed in this study genome-wide gene expression profiles of 15 metastatic lesions from three organs (bone, lung and liver) in a mouse model with multi-organ metastasis properties of human non-small cell lung cancer cells (ACC-LC319/ bone2), using a combination of laser-microbeam microdissection and DNA microarrays. We identified 299 genes that could potentially be involved in the organ-selective nature of lung cancer metastasis. Among them, 77 were bone-specifically expressed elements, including genes involved in cell adhesion, cytoskeleton/cell motility, extracellular matrix remodeling and cell-cell signaling as well as genes already known to be involved in the bone metastasis of breast cancers. Quantitative RT-PCR confirmed the specific upregulation of eight genes in bone metastasis tumors, suggesting that these genes may be involved in bone metastasis. Our findings should be helpful for a better understanding of the molecular aspects of the metastatic process in different organs, and could lead to molecular target-based anticancer drugs and prevention of metastasis, especially bone metastasis.

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Role of soluble guanylyl cyclase–cyclic GMP signaling in tumor cell proliferation

Cited by 63 publications

References 39 publications

Methylene Blue for Distributive Shock: A Potential New Use of an Old Antidote

Methylene Blue for Distributive Shock: A Potential New Use of an Old Antidote

Cobinamides Are Novel Coactivators of Nitric Oxide Receptor That Target Soluble Guanylyl Cyclase Catalytic Domain

Identification of genes potentially involved in bone metastasis by genome-wide gene expression profile analysis of non-small cell lung cancer in mice

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